|Summary sheet: 4-FMA|
|Psychoactive class||Stimulant / Entactogen|
|Routes of Administration|
4-Fluoromethamphetamine (also known as 4-FMA) is a lesser-known novel stimulant-entactogen substance of the amphetamine class. 4-FMA is chemically related to 4-FA and methamphetamine. Little is known about its pharmacology, but it likely produces its effects by increasing levels of dopamine, norepinephrine, and serotonin in the brain.
4-FMA was first detected being sold in Japan as a legal high in 2006. It has been sold online as a research chemical alongside 2-fluoroamphetamine (2-FA), 3-fluoroamphetamine (3-FA) and 4-fluoroamphetamine (4-FA). When 4-FA was made illegal in the Netherlands in 2017, 4-FMA grew in popularity as a legal substitute, due to their similar names and effects. In 2018, the number of analyzed 4-FA samples increasingly contained 4-FMA (and/or other fluorinated amphetamines) and the availability of actual 4-FA decreased sharply.
User reports describe the effects of 4-FMA as having characteristics of both traditional stimulants like amphetamine and entactogens like MDMA. Its effects have been described as subjectively lying between 4-FA and 2-FMA. It has been reported to be more likely to produce side effects like headaches and cardiovascular effects than similar substances.
Very little is known about the pharmacological properties, metabolism, and toxicity of 4-FMA. 4-FMA use may produce dependence and abuse as well as damage to the brain and other organs. It is highly advised to use harm reduction practices if using this substance.
4-Fluoromethamphetamine (4-FMA) is a synthetic molecule of the substituted amphetamine family. Molecules of this class contain a phenethylamine core featuring a phenyl ring bound to an amino (NH2) group through an ethyl chain with an additional methyl substitution at Rα. The term "amphetamine" is the contracted form of alpha-methylphenethylamine. 4-fluoromethamphetamine contains a fluorine atom at R4 of its phenyl ring and is therefore a fluorinated analogue of methamphetamine.
Similar to its structural analog 4-FA, 4-Fluoromethamphetamine is thought to act as a releasing agent and reuptake inhibitor of dopamine, serotonin, and norepinephrine, producing stimulating amphetamine-like effects at lower doses and more euphoric, entactogen effects similar to MDA at dosages above 125mg.[avoid opinion] Researchers have found some evidence that indicates some similarities between the "Serotonin Release" of 4-FMA and other popular empathogens such as: MDA, 4-Methylmethcathinone, and 4-fluoroamphetamine..
The mechanism of action of 4-FMA effectively boosts the levels of the norepinephrine, dopamine, and serotonin neurotransmitters in higher doses in the brain by binding to and partially blocking the transporter proteins that normally clear these monoamines from the synaptic cleft. This allows dopamine, norepinephrine, and serotonin to accumulate within various regions of the brain, including its reward pathways, resulting in stimulating, euphoric and entactogenic effects.
4-FMA is a CYP450 inhibitor. It reduces the metabolism of methamphetamine, which has the effect of increasing its potency, duration and systemic toxicity while also reducing its cellular toxicity.
In low doses, 4-FMA has been reported to be a lackluster nootropic for general productivity. Such usage would be strongly discouraged however, due to the increased risks for neurotoxicity and other dangerous side-effects. The reasoning for this warning is based on the studies showing that 4-FMA is similar to MDA, and belongs to the entactogen class. Using any entactogen frequently is considered dangerous, and it is seen as unwise to take "microdoses" below the minimum dose required to experience a "roll" with members of the entactogen class. At higher dosages, it is known to become dysfunctional and recreational due to the scattering quality of its euphoria and stimulation.
Similar to MDA, MDMA, 4-FA, and other substances that produce distinct pleasurable tactile "roll"-like sensations, which is typically linked to serotonin-releasing properties, 4-FMA has been reported to be able to produce similar entactogenic effects in addition to traditional stimulant ones. Some reports suggest it tends to come with more side effects and bodily strain than other fluorinated amphetamines, explaining its lack of popularity and availability.
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
- Stimulation - The stimulation which 4-FMA presents can be described as being a mix between a typical entactogen stimulation and the stimulation style of Methamphetamine.
- Tactile enhancement - This component, relative to other fluorinated amphetamines like 2-FA or 3-FA, has been reported to be a distinct aspect of the experience.
- Physical euphoria - This effect is extremely intense when compared to its physical stimulation.
- Bodily control enhancement
- Stamina enhancement
- Pupil dilation
- Appetite suppression
- Orgasm suppression
- Dehydration
- Increased perspiration
- Increased bodily temperature
- Increased heart rate
- Temporary erectile dysfunction
- Teeth grinding
- Vibrating vision
- Restless leg syndrome
- Tremor - This effect is distinctly present at doses above 150mg
- Muscle contractions
- Dizziness
- Abnormal heartbeat
- Euphoria - This effect has been reported to occur a series of euphoric waves that recede and reappear randomly throughout the experience. It is distinctly present at dosages above 100mg.
- Empathy, affection, and sociability enhancement - Varying reports differ on the level of this effect, with some reports comparing 4-FA and others comparing MDMA.
- Immersion enhancement
- Novelty enhancement
- Increased music appreciation
- Motivation enhancement'
- Delusion - As with most potent stimulants, 4-FMA has been reported as having the capacity to produce delusional ideation. However, it is not clear if this occurs in a context unique to the effects of 4-FMA.
- Ego inflation - Some users have reported that this component is distinct, although it is not clear how it compares to other substituted and non-substituted amphetamines.
- Stamina enhancement
- Thought acceleration
- Focus enhancement
- Analysis enhancement
- Increased libido
- Time distortion - This can be described as the experience of time speeding up and passing much quicker than it usually would when sober.
- Compulsive redosing
- Paranoia - As with most strong stimulants, 4-FMA has been reported to produce states of paranoia, although it is not clear to which extent this happens relative to other stimulants and under what conditions.
- The effects which occur during the offset of a stimulant experience generally feel negative and uncomfortable in comparison to the effects which occurred during its peak. This is often referred to as a "comedown" and occurs because of neurotransmitter depletion. Its effects commonly include:
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
Toxicity and harm potential
Do not use 4-FMA if you have a history of heart-related issues or experience severe headache after its use. We have been made aware of a report released by Trimbos-instituut and Nationaal Vergiftigingen Informatie Centrum (NVIC), describing incidents of strokes after an increased use of the closely related analogue 4-FA, and there is no reason this does not apply to 4-FMA as well. In addition to the common amphetamine-like effects (agitation, anxiety, tachycardia, hypertension, chest pain et al.), serious cardio- and cerebrovascular complications have been reported, including rhythm (sinus arrhythmia, ventricular extrasystoles (bigeminy), conduction disturbances) and acute cardiac failure. Although a causal relationship has not been confirmed, when presented with a severe headache and lateralization after 4-FA usage, a medical evaluation at an emergency department should be conducted immediately. 
The toxicity and long-term health effects of recreational 4-FMA use has not been studied in any scientific context and the exact toxic dosage is unknown. This is because 4-FMA has very little history of human usage. Anecdotal evidence suggests that there do not seem to be any negative health effects attributed to simply trying this drug at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed).
The LD50 (mouse; i.p.) of 4-FMA is unknown. While 4-FA does not cause long-lasting depletion of brain serotonin unlike MDMA or 4-FA's analogs 4-CA and 4-BA, it is unknown whether this also applies to 4-FMA as well.
4-FMA is reported to be particularly caustic in comparison to other compounds and can, therefore, cause chemical burns within the nasal passage and throat if it is insufflated.
It is strongly recommended that one use harm reduction practices when using this substance.
Tolerance and addiction potential
As with other stimulants, the chronic use of 4-FMA can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.
Tolerance to many of the effects of 4-FMA develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). This is how long it takes to reduce the tolerance for the stimulating effects. Tolerance for the entactogenic effects may take a longer period to reduce. 4-FA presents cross-tolerance with all dopaminergic stimulants, meaning that after the consumption of 4-FMA all stimulants will have a reduced effect.
Abuse of compounds within the amphetamine chemical class at high dosages for prolonged periods of time can potentially result in a stimulant psychosis that may present with a variety of symptoms (e.g., paranoia, hallucinations, or delusions). A review on treatment for amphetamine, dextroamphetamine, and methamphetamine abuse-induced psychosis states that about 5–15% of users fail to recover completely. The same review asserts that, based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis. Psychosis very rarely arises from therapeutic use.
Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
- Alcohol - Drinking alcohol on stimulants is considered risky because it reduces the sedative effects of the alcohol that the body uses to gauge drunkenness. This often leads to excessive drinking with greatly reduced inhibitions, increasing the risk of liver damage and increased dehydration. The effects of stimulants will also allow one to drink past a point where they might normally pass out, increasing the risk. If you do decide to do this then you should set a limit of how much you will drink each hour and stick to it, bearing in mind that you will feel the alcohol and the stimulant less.
- GHB/GBL - Stimulants increase respiration rate allowing a higher dose of sedatives. If the stimulant wears off first then the depressant effects of the GHB/GBL may overcome the user and cause respiratory arrest.
- Opioids - Stimulants increase respiration rate allowing a higher dose of opiates. If the stimulant wears off first then the opiate may overcome the patient and cause respiratory arrest.
- Cocaine - The rewarding effects of cocaine are mediated by DAT inhibition, and an increase of exocytosis of dopamine through the cell membrane. Amphetamine reverses the direction of DAT and the direction vesicular transports within the cell by a pH mediated mechanism of displacement, thus excludes the regular mechanism of dopamine release through means of exocytosis because the effects Na+/K+ ATPase are inhibited. You will find cardiac effects with the combination of cocaine and amphetamine due to a SERT mediated mechanism from the subsequent activation of 5-HT2B, which is an effect of serotonin-related valvulopathy. Amphetamines generally cause hypertension in models of abuse, and this combination can increase the chances of syncope due to turbulent blood flow during valve operation. The rewarding mechanisms of cocaine are reversed by administration of amphetamine.
- Cannabis - Stimulants increase anxiety levels and the risk of thought loops and paranoia which can lead to negative experiences.
- Caffeine - This combination of stimulants is generally considered unnecessary and may increase strain on the heart, as well as potentially causing anxiety and physical discomfort.
- Tramadol - Tramadol and stimulants both increase the risk of seizures.
- DXM - Both substances raise heart rate, in extreme cases, panic attacks caused by these substances have led to more serious heart issues.
- Ketamine - Combining amphetamine and ketamine may result in psychoses that resemble schizophrenia, but not worse than the psychoses produced by either substance alone, but this is debatable. This is due to amphetamines ability to attenuated the disruption of working memory caused by ketamine. Amphetamine alone may result in grandiosity, paranoia, or somatic delusions with little to no effect on negative symptoms. Ketamine, however, will result in thought disorders, disruption of executive functioning, and delusions due to a modification of conception. These mechanisms are due to an increase of dopaminergic activity in the mesolimbic pathway caused by amphetamine due to its pharmacology effecting dopamine, and due to a disruption of dopaminergic functioning in the mesocortical pathways via NMDA antagonism effects of ketamine. Combining the two, you may expect mainly thought disorder along with positive symptoms.
- PCP - Increases risk of tachycardia, hypertension, and manic states.
- Methoxetamine - Increases risk of tachycardia, hypertension, and manic states.
- Psychedelics (e.g. LSD, mescaline, psilocybin) - Increases risk of anxiety, paranoia, and thought loops.
- 25x-NBOMe - Amphetamines and NBOMes both provide considerable stimulation that when combined they can result in tachycardia, hypertension, vasoconstriction and, in extreme cases, heart failure. The anxiogenic and focusing effects of stimulants are also not good in combination with psychedelics as they can lead to unpleasant thought loops. NBOMes are known to cause seizures and stimulants can increase this risk.
- 2C-T-x - Suspected of mild MAOI properties. May increase the risk of hypertensive crisis.
- 5-MeO-xxT - Suspected of mild MAOI properties. May increase the risk of hypertensive crisis.
- aMT - aMT has MAOI properties which may interact unfavorably with amphetamines.
- MAOIs - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably. MAO-A inhibitors with amphetamine can lead to hypertensive crises.
This legality section is a stub.
As such, it may contain incomplete or wrong information. You can help by expanding it.
- Australia: 4-FMA is a Schedule 9 prohibited substance in Australia under the Poisons Standard (February 2021). A Schedule 9 substance is defined as a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.
- Austria: 4-FMA is illegal to possess, produce and sell under the NPSG (Neue-Psychoaktive-Substanzen-Gesetz Österreich).
- Canada: 4-FMA would be considered Schedule I as it is an analogue of Amphetamine.
- China: As of October 2015 4-FMA is a controlled substance in China.
- Germany: 4-FMA is controlled under Anlage II BtMG (Narcotics Act, Schedule II) as of July 26, 2012. It is illegal to manufacture, possess, import, export, buy, sell, procure or dispense it without a license.
- New Zealand: 4-FMA is an amphetamine analogue, so is a Schedule 3 controlled substance in New Zealand.
- Switzerland: 4-FMA is a controlled substance specifically named under Verzeichnis E.
- United Kingdom: 4-FMA is a Class A drug under the Misuse of Drugs Act. 4-FMA is covered by the 1977 addition to the Misuse of Drugs Act of 1971.
- Italy: 4-FMA is a Schedule I controlled substance.
- ↑ Nagashima, M., Seto, T., Takahashi, M., Suzuki, J., Yasuda, I. (2006). "Spectrum Data of the 3rd Governor-designated Drugs and the Analyses of Uncontrolled Drugs Purchased". Annu. Rep. Tokyo Metr. Inst. Public Health. 57: 109–113.
- ↑ Nagai, F., Nonaka, R., Satoh Hisashi Kamimura, K. (22 March 2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". European Journal of Pharmacology. 559 (2–3): 132–137. doi:10.1016/j.ejphar.2006.11.075. ISSN 0014-2999.
- ↑ Rösner, P., Quednow, B., Girreser, U., Junge, T. (10 March 2005). "Isomeric fluoro-methoxy-phenylalkylamines: a new series of controlled-substance analogues (designer drugs)". Forensic Science International. 148 (2–3): 143–156. doi:10.1016/j.forsciint.2004.05.003. ISSN 0379-0738.
- ↑ https://www.drugs-test.nl/nieuws-detail/?bericht=92
- ↑ (Annual Report 2018, section: 4-FA)
- ↑ Rickli, A., Hoener, M. C., Liechti, M. E. (March 2015). "Monoamine transporter and receptor interaction profiles of novel psychoactive substances: para-halogenated amphetamines and pyrovalerone cathinones". European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology. 25 (3): 365–376. doi:10.1016/j.euroneuro.2014.12.012. ISSN 1873-7862.
- ↑ Fuller, R. W., Baker, J. C., Perry, K. W., Molloy, B. B. (1 October 1975). "Comparison of 4-chloro-, 4-bromo- and 4-fluoroamphetamine in rats: Drug levels in brain and effects on brain serotonin metabolism". Neuropharmacology. 14 (10): 739–746. doi:10.1016/0028-3908(75)90099-4. ISSN 0028-3908.
- ↑ Nagai, F., Nonaka, R., Satoh Hisashi Kamimura, K. (22 March 2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". European Journal of Pharmacology. 559 (2): 132–137. doi:10.1016/j.ejphar.2006.11.075. ISSN 0014-2999.
- ↑ Cherner, M., Bousman, C., Everall, I., Barron, D., Letendre, S., Vaida, F., Atkinson, J. H., Heaton, R., Grant, I., Group, T. H. (September 2010). "Cytochrome P450-2D6 extensive metabolizers are more vulnerable to methamphetamine-associated neurocognitive impairment: Preliminary findings". Journal of the International Neuropsychological Society. 16 (5): 890–901. doi:10.1017/S1355617710000779. ISSN 1469-7661.
- ↑ peskypenguins (2016), 4-FMA short response
- ↑ Voor mentale gezondheid
- ↑ Vergiftigingen.info - Home
- ↑ https://psychonautwiki.org/wiki/File:Behandeling-4-fa-intoxicatie.pdf
- ↑ 14.0 14.1 14.2 Shoptaw, S. J., Kao, U., Ling, W. (21 January 2009). Cochrane Drugs and Alcohol Group, ed. "Treatment for amphetamine psychosis". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD003026.pub3. ISSN 1465-1858.
- ↑ Hofmann, F. G. (1983). A handbook on drug and alcohol abuse: the biomedical aspects (2nd ed ed.). Oxford University Press. ISBN 9780195030563.
- ↑ http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf
- ↑ Greenwald, M. K., Lundahl, L. H., Steinmiller, C. L. (December 2010). "Sustained Release d-Amphetamine Reduces Cocaine but not 'Speedball'-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine/Heroin Polydrug Abusers". Neuropsychopharmacology. 35 (13): 2624–2637. doi:10.1038/npp.2010.175. ISSN 0893-133X.
- ↑ Siciliano, C. A., Saha, K., Calipari, E. S., Fordahl, S. C., Chen, R., Khoshbouei, H., Jones, S. R. (10 January 2018). "Amphetamine Reverses Escalated Cocaine Intake via Restoration of Dopamine Transporter Conformation". The Journal of Neuroscience. 38 (2): 484–497. doi:10.1523/JNEUROSCI.2604-17.2017. ISSN 0270-6474.
- ↑ Krystal, J. H., Perry, E. B., Gueorguieva, R., Belger, A., Madonick, S. H., Abi-Dargham, A., Cooper, T. B., MacDougall, L., Abi-Saab, W., D’Souza, D. C. (1 September 2005). "Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine: Implications for Glutamatergic and Dopaminergic Model Psychoses and Cognitive Function". Archives of General Psychiatry. 62 (9): 985. doi:10.1001/archpsyc.62.9.985. ISSN 0003-990X.
- ↑ 20.0 20.1 Poisons Standard February 2021
- ↑ Branch, L. S. (2022), Consolidated federal laws of Canada, Controlled Drugs and Substances Act
- ↑ "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Retrieved 1 October 2015.
- ↑ "Anlage II BtMG" (in German). Bundesministerium der Justiz und für Verbraucherschutz. Retrieved December 19, 2019.
- ↑ "Sechsundzwanzigste Verordnung zur Änderung betäubungsmittelrechtlicher Vorschriften" (in German). Bundesanzeiger Verlag. Retrieved December 19, 2019.
- ↑ "§ 29 BtMG" (in German). Bundesministerium der Justiz und für Verbraucherschutz. Retrieved December 19, 2019.
- ↑ Misuse of Drugs Act 1975 No 116 (as at 01 July 2022), Public Act – New Zealand Legislation
- ↑ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020.
- ↑ Tabella delle sostanze stupefacenti e psicotrope (in italian), Tabella 1, pagina 3